Vitamin K deficiency bleeding in Great Britain and Ireland: British Paediatric Surveillance Unit Surveys, 1993 94 and 2001-02.

OBJECTIVE: To conduct and report monitoring of vitamin K deficiency bleeding (VKDB) in Great Britain and Ireland following the 1988-90 survey (VKDB-90). DESIGN: Two 2-year surveys conducted during 1993-4 (VKDB-94) and 2001-02 (VKDB-02). SETTING: Data collected from all consultant paediatricians in Great Britain and Ireland. PATIENTS: All infants presenting with bleeding resulting from vitamin K (VK) deficiency. MAIN OUTCOME MEASURES: Incidence of VKDB, related mortality/morbidity and VK prophylaxis recommended/received, noting predisposing features. RESULTS: Compared with previous studies, VKDB-02 found fewer cases of VKDB (RR: 0.27 (95% CI: 0.12 to 0.59), p<0.001) with no deaths, no long-term morbidity and reduced incidence among those receiving any oral dosing (RR: 0.24 (95% CI: 0.06 to 1.01), p<0.059). Breast-fed infants accounted for the vast majority of cases. The number receiving no prophylaxis fell consecutively over time: 20 of 27 in VKDB-90, 10 of 32 in VKDB-94 and 4 (because of parental refusal) of 7 in VKDB-02. Seven received one oral dose of VK in VKDB-90, 16 in VKDB-94 and none in VKDB-02. Underlying liver disease was found in six cases in VKDB-90, 12 in VKDB-94 and one in VKDB-02. CONCLUSIONS: In the most recent survey, the incidence of VKDB was about one third that in the two earlier studies. Late onset VKDB remains virtually confined to breast-fed infants who have received either no VK or just one oral dose. The effectiveness of oral prophylaxis regimens has improved over the last 15 years, but parental refusal of prophylaxis has become more problematic.     

Neonatal vitamin K prophylaxis in Great Britain and Ireland: the impact of perceived risk and product licensing on effectiveness

Objective

To determine current use of vitamin K (VK) prophylaxis in newborns and review the efficacy and effectiveness of regimens used.

Design

Efficacy and effectiveness calculated using current practice details, data from Southern Ireland and two previous surveys, together with contemporaneous studies of vitamin K deficiency bleeding (VKDB).

Setting

Current survey: United Kingdom (Great Britain and Northern Ireland). Efficacy and effectiveness tables: United Kingdom and Southern Ireland.

Main outcome measures

Current VK prophylaxis following uncomplicated term deliveries. Relative risk of VKDB calculated for the VK actually received and for “intention to treat”.

Results

Questionnaire response rate 95% (n = 243), all recommending VK prophylaxis. No association between unit size and route of administration. For uncomplicated term deliveries, 60% recommended intramuscular (IM) prophylaxis, 24% oral and 16% offered both routes without bias. All units offering IM gave a single dose, mostly 1 mg Konakion Neonatal. Oral regimens showed more variation: two thirds gave 2 mg (range 0.5–2 mg), the number of doses ranged from 1 to 11 and many used preparations off‐licence or the unlicensed Orakay. IM prophylaxis, if given, provided the best protection (most efficacious) against VKDB. However, on an intention‐to‐treat basis (effectiveness), there is no statistically significant difference between the risks of VKDB after intended IM VK and after oral prophylaxis intended to continue beyond a week.

Conclusions

Although the principles of VK prophylaxis is now accepted by all, there is no uniformity in practice. Omission of prophylaxis appears to be a greater problem for IM than for multi‐dose oral prophylaxis, affecting overall effectiveness.     

Vitamin K prophylaxis and vitamin K deficiency bleeding (VKDB) in early infancy

The efficacy of vitamin K prophylaxis (1 mg im or sc, or 1-2 mg orally both given as a single dose at birth) in the prevention of vitamin K deficiency bleeding in early infancy was estimated in Germany during a 15-month period between 1988 and 1989. Cases were identified by a survey of all paediatric hospitals and population denominators by a survey of all obstetric hospitals. Response rates were 85% and 68%, respectively. Thirteen cases of vitamin K deficiency bleeding in early infancy with confirmed prophylactic states were confirmed, seven of whom had intracranial haemorrhage. The estimated efficacy of single parenteral administration of vitamin K versus no prophylaxis was 96.7% (95% confidence interval: 74-99.6%) and for single oral administration versus no prophylaxis 80.4% (9.1-95.6%). Single parenteral vitamin K prophylaxis gave substantial protection against vitamin K deficiency bleeding in early infancy. Single oral prophylaxis appeared to be less effective, although the difference was not significant, as indicated by the wide overlap of the respective 95% confidence intervals.     

Vitamin K prophylaxis and late vitamin K deficiency bleeding in infants: Fifth nationwide survey in Japan

Background: In 1980, the first nationwide survey on late vitamin K deficiency bleeding (VKDB) in infants was conducted in Japan, and it was followed by the second, third and fourth nationwide surveys in 1985, 1988 and 1991, respectively. The fifth nationwide survey was designed to ascertain the epidemiology of late VKDB between January 1999 and December 2004. Patients and methods: Questionnaires were sent to 2161 hospitals in Japan that employed members of the Japan Pediatric Society in March 2005. Responses were received from 1373 hospitals, for a response rate of 63.5%. Results: The total number of reported cases was 71, including 21 idiopathic type and 16 secondary type. The incidence of late VKDB was estimated to be 1.9 cases per 100 000 births (95% confidence interval: 1.2–3.0) during this survey period. In 34 cases, the presence or absence of any underlying disease was not clarified. A total of 67/71 infants were entirely breast‐fed. Intracranial hemorrhaging was observed in 26 (63.4%) out of 41 infants whose bleeding sites were described in the questionnaires. In 63 cases (88.7%) of late VKDB found in the present survey, however, vitamin K had been given at least once either during or after the neonatal period. Conclusions: A reevaluation of the current prophylaxis strategy for late VKDB in infants is necessary.     

New Zealand surveillance of neonatal vitamin K deficiency bleeding (VKDB): 1998-2008

Aim: To undertake surveillance of vitamin K deficiency bleeding (VKDB) from 1998, through the transition to a new single licensed vitamin K preparation in 2001, to 2008. Methods: VKDB was listed with other rare conditions on the card sent monthly to registered specialist paediatricians by the New Zealand Paediatric Surveillance Unit with a request to indicate whether or not a case had been seen in the previous month. Those notifying a case were sent a two‐page questionnaire. The main outcome measures were incidence of VKDB of early (first day of life), classic (days 2–7) and late‐onset (day 8 to 6 months) type; related morbidity and mortality; receipt of vitamin K; and predisposing factors. Results: Response rate of return of surveillance cards was high, averaging 94.5%. There were 35 notifications of which 23 were valid cases. Seventeen cases met criteria for confirmed VKDB, two for ‘probable’ and four for ‘possible’. There were eight confirmed classic cases with an overall incidence of 1.24 (95% confidence interval 0.54–2.45) per 100 000 births; none had received vitamin K prophylaxis, seven were fully breastfed and all fully recovered. There were nine confirmed late‐onset cases with an overall incidence of 1.40 (95% confidence interval 0.64–2.65) per 100 000 births; eight had received no vitamin K, eight were fully breastfed, six had liver disease, four suffered an intracranial haemorrhage and one died. Conclusions: In New Zealand, VKDB is virtually confined to fully breastfed infants not given vitamin K at birth. Late‐onset cases were frequently associated with liver disease.     

Early vitamin K deficiency bleeding after maternal phenobarbital intake: management of massive intracranial haemorrhage by minimal surgical intervention

Vitamin K deficiency bleeding within the first 24 h of life is caused in most cases by maternal drug intake (e.g. coumarins, anticonvulsants, tuberculostatics) during pregnancy. Haemorrhage is often life-threatening and usually not prevented by vitamin K prophylaxis at birth. We report a case of severe intracranial bleeding at birth secondary to phenobarbital-induced vitamin K deficiency and traumatic delivery. Burr hole trepanations of the skull were performed and the subdural haematoma was evacuated. Despite the severe prognosis, the infant showed an unexpected good recovery. At the age of 3 years, neurological examinations were normal as was the EEG at the age of 9 months. CT showed close to normal intracranial structures. Conclusion This case report stresses the importance of antenatal vitamin K prophylaxis and the consideration of a primary Caesarean section in maternal vitamin K deficiency states and demonstrates the successful management of massive subdural haemorrhage by a limited surgical approach. Received: 4 July 1997 and in revised form: 30 October 1997 / Accepted: 7 November 1997     

Late vitamin K deficiency bleeding in infants: five-year prospective study

ObjectiveTo study the presenting clinical and demographic features, risk factors, and outcome of infants with late vitamin K deficiency bleeding.MethodsOver a 5-year study period, the presenting clinical features and outcome of all 47 infants observed aged less than 6 months, who were diagnosed with late-onset primary and secondary VKDB by detailed history, physical examination, and laboratory findings were evaluated. Confirmed primary late VKDB was diagnosed when no cause other than breastfeeding could be found, while in the secondary subtype additional risk factors compromising the vitamin K effect were diagnosed.ResultsSecondary late VKDB (83%, 39 patients) was more common than the primary subtype. The mean age of patients was 10.50 ± 5.75 and 9.74 ± 6.04 weeks in primary and secondary VKDB subtypes, respectively, and the age of infants did not have a significant difference (p > 0.05). The male to female ratio was 2.13:1. The residency, place and mode of delivery, gestational age, and types of feeding of patients did not have a significant difference between VKDB subtypes. The skin and gastrointestinal tract (GIT) (40.4%) followed by intracranial hemorrhage (ICH) (32%), were common sites of bleeding. Neurological complications were seen in 21% of patients; however, lethality was 23%, and the outcome of patients did not have a significant difference (p > 0.05) between VKDB subtypes.ConclusionSecondary late VKDB is more common than the primary subtypes, and late VKDB is still a serious disease in developing countries, including Iraq, when vitamin K prophylaxis isn’t routinely used at birth.     

Vitamin K supplementation to prevent hemorrhagic morbidity and mortality of newborns in India and China

Background

Vitamin K deficiency bleeding (VKDB) can cause prolonged and bleeding (intracranial hemorrhage) among newborns, which can be life-threatening or lead to long-term morbidity. The aim of this review article is to reiterate empirical evidence to support the argument that vitamin K should be mandatory for newborns in India and China, as well as in other countries with a high burden of neonatal deaths.

Data sources

Studies were integrated from the PubMed/MEDLINE database search, as well as related literature available elsewhere.

Results

Both India and China have been slow in adopting an effective program for administering vitamin K injections to newborns to prevent VKDB-related morbidity and mortality. VKDB cases in China and India have shown inadequate attention to routine use of vitamin K by injection.

Conclusions

While no reliable data are publicly available, the issue of VKDB is at last receiving some attention from the Chinese public health system as well as the Indian government. In both countries, routine vitamin K administration to newborns would prove to be a cost-effective intervention to reduce preventable neonatal morbidity and mortality. VKDB is a global neonatal care issue, including countries where parental resistance is preventing babies from defense against this life-threatening condition.

     

低体重早产儿维生素K缺乏与脑室出血的关系

目的　研究低体重早产儿维生素K缺乏状况及其与脑室出血的相关性。方法　采用酶联免疫吸附法 (ELISA)检测 5 4例孕周 <34周、体质量 90 4～ 2 15 7g早产儿静脉血凝血酶原前体蛋白 (PIVKA Ⅱ ) ,并于生后3～ 5d行头颅B超检查 ,诊断有无脑室出血。结果　PIVKA Ⅱ阳性 17例 ,低体重早产儿维生素K缺乏发生率为 31.5 % (17/ 5 4 ) ,低体重早产儿脑室出血发生率为 4 8.7% (19/ 39) ,维生素K缺乏并脑室出血 4例 ,其中重度脑室出血 3例。窒息、低出生体重是主要致病因素。结论　低体重早产儿存在维生素K缺乏 ,相当一部分早产儿存在脑室出血 ,维生素K缺乏虽不是脑室出血的主要致病因素 ,但其他致病因素也可能加重脑室出血的严重程度 ,应予重视     

Vitamin A deficiency and child feeding in Beijing and Guizhou, China

Background  Vitamin A deficiency (VAD) is one of the three major micronutrient deficiencies in the world. In order to investigate the status of VAD and child feeding in China, we conducted the survey in Beijing city and Guizhou province. Methods  We included a high socioeconomic area (Beijing) and a low socioeconomic area (Guizhou province) in China in our study. Participants included 1236 randomly selected children aged 0-71 months from stratified clusters (628 in Beijing and 608 in Guizhou), 409 from urban and 827 from rural areas. A food intake frequency questionnaire was used for dietary assessment. Fluorescence microanalysis was carried out to measure serum retinol concentrations. Serum retinol cut-off values of less than 20 μg/dl and 30 μg/dl were defined as sub-clinical VAD and suspected sub-clinical VAD, respectively. Results  No xerophthalmia or night blindness was found. The mean concentration of serum retinol was 31.5 μg/dl in the high socioeconomic group, and 26.5 μg/dl in the low socioeconomic group. Rural infants had lower concentrations of serum retinol compared with the urban ones (26.9±8.1 μg/dl vs 31.8±7.3 μg/dl). The prevalence of sub-clinical VAD among all the children was 7.8%, and increased to 15.7% in children from the low socioeconomic group. In infants from the high socioeconomic area, the prevalence of suspected subclinical VAD was 38.0%, increasing to 59.5% in infants from the low socioeconomic area. The children from the low socioeconomic area had significantly lower frequency of intake of meat than the children in other groups. The prevalence of suspected sub-clinical VAD was higher in the children with lower consumption frequency of vitamin A rich foods than the children with higher consumption frequency of vitamin A rich foods. Conclusions  VAD appears to be a moderate public health problem in certain areas of China. In areas with low socioeconomic status, VAD in childrean is more severe, and infants may be the group at the highest risk for VAD. Inadequate intake of vitamin A rich foods may result in VAD. A comprehensive long-term national strategy needs to be fostered in China for the treatment and prevention of the deficiency.     

Prevention of vitamin K deficiency bleeding with oral mixed micellar phylloquinone: results of a 6-year surveillance in Switzerland

In 1995, a new form of vitamin K prophylaxis with two oral doses of 2 mg mixed micellar phylloquinone (Konakion MM) on the 1st and 4th day of life was introduced in Switzerland. It was hoped that this new galenic preparation of phylloquinone would protect infants with insufficient or absent bile acid excretion from late vitamin K deficiency bleeding (VKDB). Subsequently, the occurrence of VKDB was monitored prospectively between July 1, 1995 and June 30, 2001 with the help of the Swiss Paediatric Surveillance Unit (SPSU). Over a period of 6 years (475,000 deliveries), there were no cases of early (<24 h of age), one case of classical (2–7 days of life), and 18 cases of late (1–12 weeks) VKDB fulfilling standard case definitions. In 13/18 patients with late VKDB there was pre-existing liver disease and in 4/18 patients, parents had refused prophylaxis. The incidence of late VKDB for infants with completed Konakion MM prophylaxis was 2.31/100,000 (95% CI: 1.16–4.14) and for the entire population 3.79/100,000 (95% CI: 2.24–5.98). There was only one case of late VKDB after complete prophylaxis in an infant without underlying liver disease. Conclusion: two oral doses of 2 mg of a mixed micellar vitamin K preparation failed to abolish VKDB. The recommendations for vitamin K prophylaxis in Switzerland have therefore been changed to include a third dose at 4 weeks of age. Starting on January 1, 2004, the incidence of vitamin K deficiency bleeding will again be monitored prospectively by the Swiss Paediatric Surveillance Unit.Abbreviations CI confidence interval - SPSU Swiss Paediatric Surveillance Unit - VKDB vitamin K deficiency bleeding